MYLK_RABIT
ID MYLK_RABIT Reviewed; 1147 AA.
AC P29294; Q28729;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Myosin light chain kinase, smooth muscle;
DE Short=MLCK;
DE Short=smMLCK;
DE EC=2.7.11.18;
DE AltName: Full=Telokin;
DE Contains:
DE RecName: Full=Myosin light chain kinase, smooth muscle, deglutamylated form;
GN Name=MYLK;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Smooth muscle;
RX PubMed=1748666; DOI=10.1016/s0021-9258(18)54375-1;
RA Gallagher P.J., Herring B.P., Griffin S.A., Stull J.T.;
RT "Molecular characterization of a mammalian smooth muscle myosin light chain
RT kinase.";
RL J. Biol. Chem. 266:23936-23944(1991).
RN [2]
RP ERRATUM OF PUBMED:1748666.
RX PubMed=1577772; DOI=10.1016/s0021-9258(19)50444-6;
RA Gallagher P.J., Herring B.P., Griffin S.Z., Stull J.T.;
RL J. Biol. Chem. 267:9450-9450(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 3), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Smooth muscle;
RX PubMed=1748667; DOI=10.1016/s0021-9258(18)54376-3;
RA Gallagher P.J., Herring B.P.;
RT "The carboxyl terminus of the smooth muscle myosin light chain kinase is
RT expressed as an independent protein, telokin.";
RL J. Biol. Chem. 266:23945-23952(1991).
RN [4]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND CALMODULIN-BINDING.
RX PubMed=11113114; DOI=10.1074/jbc.m005270200;
RA Birukov K.G., Csortos C., Marzilli L., Dudek S., Ma S.-F., Bresnick A.R.,
RA Verin A.D., Cotter R.J., Garcia J.G.N.;
RT "Differential regulation of alternatively spliced endothelial cell myosin
RT light chain kinase isoforms by p60(Src).";
RL J. Biol. Chem. 276:8567-8573(2001).
CC -!- FUNCTION: Calcium/calmodulin-dependent myosin light chain kinase
CC implicated in smooth muscle contraction via phosphorylation of myosin
CC light chains (MLC). Also regulates actin-myosin interaction through a
CC non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains.
CC Involved in the inflammatory response (e.g. apoptosis, vascular
CC permeability, leukocyte diapedesis), cell motility and morphology,
CC airway hyperreactivity and other activities relevant to asthma.
CC Required for tonic airway smooth muscle contraction that is necessary
CC for physiological and asthmatic airway resistance. Necessary for
CC gastrointestinal motility. Implicated in the regulation of endothelial
CC as well as vascular permeability, probably via the regulation of
CC cytoskeletal rearrangements. In the nervous system it has been shown to
CC control the growth initiation of astrocytic processes in culture and to
CC participate in transmitter release at synapses formed between cultured
CC sympathetic ganglion cells. Critical participant in signaling sequences
CC that result in fibroblast apoptosis. Plays a role in the regulation of
CC epithelial cell survival. Required for epithelial wound healing,
CC especially during actomyosin ring contraction during purse-string wound
CC closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5
CC channel activity in a calcium-dependent signaling, by inducing its
CC subcellular localization at the plasma membrane. Promotes cell
CC migration (including tumor cells) and tumor metastasis. PTK2B/PYK2
CC activation by phosphorylation mediates ITGB2 activation and is thus
CC essential to trigger neutrophil transmigration during acute lung injury
CC (ALI). May regulate optic nerve head astrocyte migration. Probably
CC involved in mitotic cytoskeletal regulation. Regulates tight junction
CC probably by modulating ZO-1 exchange in the perijunctional actomyosin
CC ring. Mediates burn-induced microvascular barrier injury; triggers
CC endothelial contraction in the development of microvascular
CC hyperpermeability by phosphorylating MLC. Essential for intestinal
CC barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial
CC barrier function during giardiasis intestinal infection via
CC reorganization of cytoskeletal F-actin and tight junctional ZO-1.
CC Necessary for hypotonicity-induced Ca(2+) entry and subsequent
CC activation of volume-sensitive organic osmolyte/anion channels (VSOAC)
CC in cervical cancer cells (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[myosin light chain] = ADP + H(+) + O-phospho-L-
CC seryl-[myosin light chain]; Xref=Rhea:RHEA:22004, Rhea:RHEA-
CC COMP:13684, Rhea:RHEA-COMP:13685, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[myosin light chain] = ADP + H(+) + O-
CC phospho-L-threonyl-[myosin light chain]; Xref=Rhea:RHEA:53900,
CC Rhea:RHEA-COMP:13686, Rhea:RHEA-COMP:13687, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977,
CC ChEBI:CHEBI:456216; EC=2.7.11.18;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC -!- ACTIVITY REGULATION: All catalytically active isoforms require binding
CC to calcium and calmodulin for activation.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.2 uM for MLC (isoform Smooth-muscle at 22 degrees Celsius)
CC {ECO:0000269|PubMed:11113114};
CC Vmax=17.0 umol/min/mg enzyme (isoform Smooth-muscle at 22 degrees
CC Celsius) {ECO:0000269|PubMed:11113114};
CC -!- SUBUNIT: All isoforms including Telokin bind calmodulin. Interacts with
CC SVIL (By similarity). Interacts with CTTN; this interaction is reduced
CC during thrombin-induced endothelial cell (EC) contraction but is
CC promoted by the barrier-protective agonist sphingosine 1-phosphate
CC (S1P) within lamellipodia. A complex made of ABL1, CTTN and MYLK
CC regulates cortical actin-based cytoskeletal rearrangement critical to
CC sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier
CC enhancement. Binds to NAA10/ARD1 and PTK2B/PYK2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q15746}. Cell
CC projection, lamellipodium {ECO:0000250|UniProtKB:Q15746}. Cleavage
CC furrow {ECO:0000250|UniProtKB:Q15746}. Cytoplasm, cytoskeleton, stress
CC fiber {ECO:0000250|UniProtKB:Q15746}. Note=Localized to stress fibers
CC during interphase and to the cleavage furrow during mitosis.
CC {ECO:0000250|UniProtKB:Q15746}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1; Synonyms=Smooth-muscle;
CC IsoId=P29294-1; Sequence=Displayed;
CC Name=3; Synonyms=Telokin;
CC IsoId=P29294-3; Sequence=VSP_018849;
CC -!- TISSUE SPECIFICITY: Isoform Telokin is found in all smooth muscle
CC tested except the aorta. It is not present in non-muscle tissue.
CC {ECO:0000269|PubMed:1748667}.
CC -!- PTM: The C-terminus is deglutamylated by AGTPBP1/CCP1, AGBL1/CCP4 and
CC AGBL4/CCP6, leading to the formation of Myosin light chain kinase,
CC smooth muscle, deglutamylated form. The consequences of C-terminal
CC deglutamylation are unknown (By similarity). {ECO:0000250}.
CC -!- PTM: Can probably be down-regulated by phosphorylation. Tyrosine
CC phosphorylation by ABL1 increases kinase activity, reverses MLCK-
CC mediated inhibition of Arp2/3-mediated actin polymerization, and
CC enhances CTTN-binding. Phosphorylation by SRC promotes CTTN binding (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 3]: Has no catalytic activity. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; M76233; AAA73093.1; -; mRNA.
DR EMBL; M76234; AAA31408.1; -; Genomic_DNA.
DR EMBL; M76181; AAA31409.1; -; mRNA.
DR PIR; A41675; A41675.
DR PIR; A59307; A59307.
DR RefSeq; NP_001075775.1; NM_001082306.1.
DR AlphaFoldDB; P29294; -.
DR SMR; P29294; -.
DR iPTMnet; P29294; -.
DR PRIDE; P29294; -.
DR GeneID; 100009143; -.
DR KEGG; ocu:100009143; -.
DR CTD; 4638; -.
DR eggNOG; KOG0613; Eukaryota.
DR InParanoid; P29294; -.
DR OrthoDB; 330091at2759; -.
DR BRENDA; 2.7.11.18; 1749.
DR SABIO-RK; P29294; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0032154; C:cleavage furrow; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004687; F:myosin light chain kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR CDD; cd00063; FN3; 1.
DR CDD; cd14191; STKc_MLCK1; 1.
DR Gene3D; 2.60.40.10; -; 4.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR015725; MLCK1_kinase_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF07679; I-set; 3.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00060; FN3; 1.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative promoter usage; ATP-binding; Calcium;
KW Calmodulin-binding; Cell projection; Cytoplasm; Cytoskeleton;
KW Disulfide bond; Immunoglobulin domain; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..1147
FT /note="Myosin light chain kinase, smooth muscle"
FT /id="PRO_0000024357"
FT CHAIN 1..1142
FT /note="Myosin light chain kinase, smooth muscle,
FT deglutamylated form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000403733"
FT REPEAT 100..111
FT /note="1"
FT REPEAT 112..123
FT /note="2"
FT REPEAT 124..132
FT /note="3; truncated"
FT REPEAT 133..144
FT /note="4"
FT REPEAT 145..156
FT /note="5"
FT REPEAT 157..168
FT /note="6"
FT REPEAT 169..180
FT /note="7"
FT REPEAT 181..192
FT /note="8"
FT REPEAT 193..204
FT /note="9"
FT REPEAT 205..216
FT /note="10"
FT REPEAT 217..228
FT /note="11"
FT REPEAT 229..240
FT /note="12"
FT REPEAT 241..252
FT /note="13"
FT REPEAT 253..264
FT /note="14"
FT REPEAT 265..276
FT /note="15"
FT REPEAT 277..288
FT /note="16"
FT DOMAIN 329..417
FT /note="Ig-like C2-type 1"
FT DOMAIN 469..557
FT /note="Ig-like C2-type 2"
FT DOMAIN 565..657
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 696..951
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 1041..1130
FT /note="Ig-like C2-type 3"
FT REGION 1..330
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..41
FT /note="Actin-binding"
FT /evidence="ECO:0000250"
FT REGION 26..41
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 100..288
FT /note="16 X 12 AA tandem repeats"
FT REGION 292..692
FT /note="Actin-binding (calcium/calmodulin-insensitive)"
FT /evidence="ECO:0000250"
FT REGION 424..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 644..678
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 943..1006
FT /note="Calmodulin-binding"
FT REGION 999..1019
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..27
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..317
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 999..1015
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 817
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 702..710
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 725
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 681
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 807
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 867
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 991
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 992
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 1004
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 1005
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 1008
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT MOD_RES 1010
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6PDN3"
FT MOD_RES 1011
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15746"
FT DISULFID 350..401
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 1062..1114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 1..992
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_018849"
FT CONFLICT 1114
FT /note="C -> R (in Ref. 3; AAA31409)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1147 AA; 125720 MW; F039E624C6E31024 CRC64;
MDFRANLQRQ VKPKTVSEEE RKVHSPQQVD FRSVLAKKGT PKTPVPEKAP PPKPATPDFR
SVLGSKKKLP AENGSSNAEA LNVKATESPK LVGNAPLSGS LKPVANAKPA ETLKPVANTK
PAETLKPVAN AETLKPMGNA KPAESSKPVG NTKPAETLKP VGNTKPAETL KPVGNIKPAE
TLKPVGNIKP AETLKPVGNT KPTETLKPVA NAKSAETLKP IANTKPAETL KPVGNAKPAE
TLKPVGNAKP AETLKPVGNA KPAETLKPVG NAKPAETLKA VANAKPAETP KPAGKEELKK
EVQNDVNCKR EKAGAADNEK PPASPGTAPT FKEKLQDVRV AEGEKLLLQC QVSSEPPATI
TWTLNGKTLK TTKFVILSQE GSLCSVSIEK ALPEDRGLYK CVAKNAAPEA ECSCHVTVHD
APASENAKAP EMKSRRPKSS LPPVLGTESD ATVKKKPAPK TPPKAATPPQ IPQFPEDQKV
RAGERVELFG KVAGTQPITC TWMKFRKQIQ DSEHIKVENS EAGSKLTILA ARQEHCGCYT
LLVENKLGSR QAQVNLTVVD KPDPPAGTPC ASDIRSSSLT LSWYGSSYDG GSAVQSYSVE
IWDSVDKMWT ELATCRSTSF NVRDLLPDRE YKFRVRAINV YGTSEPSQES ELTTVGEKPE
EPKDEVEEVS DDDEKEPEVD YRTVTVNTEQ KVSDFYDIEE RLGSGKFGQV FRLVEKKTGK
IWAGKFFKAY SAKEKENIPA EIGIMNCLHH PKLVQCVDAF EEKANIVMVL EIVSGGELFE
RIIDEDFELT ERECIKYMRQ ISEGVEYIHK QGIVHLDLKP ENIMCVNKTG TRIKLIDFGL
ARRLENAGSL KVLFGTPEFV APEVINYEPI SYATDMWSIG VICYILVSGL SPFMGDNDNE
TLANVTSATW DFDDEAFDEI SDDAKDFISN LLKKDMKNRL DCTQCLQHPW LMKDTKNMEA
KKLSKDRMKK YMARRKWQKT GNAVRAIGRL SSMAMISGLS GRKSSTGSPT SPLTAERLET
EEDVSQAFLE AVAEEKPHVK PYFSKTIRDL EVVEGSAARF DCKIEGYPDP EVVWFKDDQS
IRESRHFQID YDEDGNCSLI ISDVCGDDDA KYTCKAVNSL GEATCTAELI VETMEEGEGE
GEEEEEE
